Skip to main content
Journal cover image

Activation of matrix metalloproteinases following anti-Aβ immunotherapy; implications for microhemorrhage occurrence.

Publication ,  Journal Article
Wilcock, DM; Morgan, D; Gordon, MN; Taylor, TL; Ridnour, LA; Wink, DA; Colton, CA
Published in: J Neuroinflammation
September 9, 2011

BACKGROUND: Anti-Aβ immunotherapy is a promising approach to the prevention and treatment of Alzheimer's disease (AD) currently in clinical trials. There is extensive evidence, both in mice and humans that a significant adverse event is the occurrence of microhemorrhages. Also, vasogenic edema was reported in phase 2 of a passive immunization clinical trial. In order to overcome these vascular adverse effects it is critical that we understand the mechanism(s) by which they occur. METHODS: We have examined the matrix metalloproteinase (MMP) protein degradation system in two previously published anti-Aβ immunotherapy studies. The first was a passive immunization study in which we examined 22 month old APPSw mice that had received anti-Aβ antibodies for 1, 2 or 3 months. The second is an active vaccination study in which we examined 16 month old APPSw/NOS2-/- mice treated with Aβ vaccination for 4 months. RESULTS: There is a significant activation of the MMP2 and MMP9 proteinase degradation systems by anti-Aβ immunotherapy, regardless of whether this is delivered through active vaccination or passive immunization. We have characterized this activation by gene expression, protein expression and zymography assessment of MMP activity. CONCLUSIONS: Since the MMP2 and MMP9 systems are heavily implicated in the pathophysiology of intracerbral hemorrhage, these data may provide a potential mechanism of microhemorrhage due to immunotherapy. Increased activity of the MMP system, therefore, is likely to be a major factor in increased microhemorrhage occurrence.

Duke Scholars

Published In

J Neuroinflammation

DOI

EISSN

1742-2094

Publication Date

September 9, 2011

Volume

8

Start / End Page

115

Location

England

Related Subject Headings

  • Nitric Oxide Synthase Type II
  • Neurology & Neurosurgery
  • Microcirculation
  • Mice, Transgenic
  • Mice
  • Matrix Metalloproteinase 9
  • Matrix Metalloproteinase 2
  • Immunotherapy
  • Humans
  • Enzyme Activation
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Wilcock, D. M., Morgan, D., Gordon, M. N., Taylor, T. L., Ridnour, L. A., Wink, D. A., & Colton, C. A. (2011). Activation of matrix metalloproteinases following anti-Aβ immunotherapy; implications for microhemorrhage occurrence. J Neuroinflammation, 8, 115. https://doi.org/10.1186/1742-2094-8-115
Wilcock, Donna M., Dave Morgan, Marcia N. Gordon, Tiffany L. Taylor, Lisa A. Ridnour, David A. Wink, and Carol A. Colton. “Activation of matrix metalloproteinases following anti-Aβ immunotherapy; implications for microhemorrhage occurrence.J Neuroinflammation 8 (September 9, 2011): 115. https://doi.org/10.1186/1742-2094-8-115.
Wilcock DM, Morgan D, Gordon MN, Taylor TL, Ridnour LA, Wink DA, et al. Activation of matrix metalloproteinases following anti-Aβ immunotherapy; implications for microhemorrhage occurrence. J Neuroinflammation. 2011 Sep 9;8:115.
Wilcock, Donna M., et al. “Activation of matrix metalloproteinases following anti-Aβ immunotherapy; implications for microhemorrhage occurrence.J Neuroinflammation, vol. 8, Sept. 2011, p. 115. Pubmed, doi:10.1186/1742-2094-8-115.
Wilcock DM, Morgan D, Gordon MN, Taylor TL, Ridnour LA, Wink DA, Colton CA. Activation of matrix metalloproteinases following anti-Aβ immunotherapy; implications for microhemorrhage occurrence. J Neuroinflammation. 2011 Sep 9;8:115.
Journal cover image

Published In

J Neuroinflammation

DOI

EISSN

1742-2094

Publication Date

September 9, 2011

Volume

8

Start / End Page

115

Location

England

Related Subject Headings

  • Nitric Oxide Synthase Type II
  • Neurology & Neurosurgery
  • Microcirculation
  • Mice, Transgenic
  • Mice
  • Matrix Metalloproteinase 9
  • Matrix Metalloproteinase 2
  • Immunotherapy
  • Humans
  • Enzyme Activation